Jamnicki-Abegg Marina, Weihrauch Dorothee, Pagel Paul S, Kersten Judy R, Bosnjak Zeljko J, Warltier David C, Bienengraeber Martin W
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Anesthesiology. 2005 Nov;103(5):1006-14. doi: 10.1097/00000542-200511000-00015.
Volatile anesthetics attenuate apoptosis. The underlying mechanisms remain undefined. The authors tested whether isoflurane reduces apoptosis in cardiomyocytes subjected to oxidative or inflammatory stress by enhancing Akt and B-cell lymphoma-2 (Bcl-2).
Adult and neonatal rat ventricular myocytes and atrial HL-1 myocytes were exposed to hypoxia, hydrogen peroxide, or neutrophils with or without isoflurane pretreatment. The authors assessed cell damage and investigated apoptosis using mitochondrial cytochrome c release, caspase activity, and TUNEL assay. They determined expression of phospho-Akt and Bcl-2 and tested their involvement by blocking phospho-Akt with wortmannin and Bcl-2 with HA14-1.
Isoflurane significantly reduced the cell damage and apoptosis induced by hypoxia, H2O2, and neutrophils. Isoflurane reduced hypoxia-induced mitochondrial cytochrome c release in HL-1 cells by 45 +/- 12% and caspase activity by 28 +/- 4%; in neonatal cells, it reduced caspase activity by 43 +/- 5% and TUNEL-positive cells by 50 +/- 2%. Isoflurane attenuated H2O2-induced caspase activity in HL-1 cells by 48 +/- 16% and TUNEL-positive cells by 78 +/- 3%; in neonatal cells, it reduced caspase activity by 30 +/- 3% and TUNEL-positive cells by 32 +/- 7%. In adult cardiomyocytes exposed to neutrophils, isoflurane decreased both mitochondrial cytochrome c and caspase activity by 47 +/- 3% and TUNEL-positive cells by 25 +/- 4%. Isoflurane enhanced phospho-Akt and Bcl-2 expression. Wortmannin and HA14-1 prevented the action of isoflurane (53 +/- 8% and 54 +/- 7% apoptotic cells vs. 18 +/- 1% without blockers).
Isoflurane protects cardiomyocytes against apoptosis induced by hypoxia, H2O2, or activated neutrophils through Akt activation and increased Bcl-2 expression. This suggests that a reduction in apoptosis contributes to the cardioprotective effects of isoflurane.
挥发性麻醉剂可减轻细胞凋亡。其潜在机制尚不清楚。作者测试了异氟烷是否通过增强Akt和B细胞淋巴瘤-2（Bcl-2）来减少遭受氧化或炎症应激的心肌细胞的凋亡。
成年和新生大鼠心室肌细胞以及心房HL-1肌细胞在有或无异氟烷预处理的情况下，暴露于缺氧、过氧化氢或中性粒细胞中。作者评估细胞损伤，并使用线粒体细胞色素c释放、半胱天冬酶活性和TUNEL检测来研究细胞凋亡。他们测定磷酸化Akt和Bcl-2的表达，并通过用渥曼青霉素阻断磷酸化Akt和用HA14-1阻断Bcl-2来测试它们的作用。
异氟烷显著减少了由缺氧、过氧化氢和中性粒细胞诱导的细胞损伤和细胞凋亡。异氟烷使HL-1细胞中缺氧诱导的线粒体细胞色素c释放减少45±12%，半胱天冬酶活性减少28±4%；在新生细胞中，它使半胱天冬酶活性减少43±5%，TUNEL阳性细胞减少50±2%。异氟烷使HL-1细胞中过氧化氢诱导的半胱天冬酶活性减少48±16%，TUNEL阳性细胞减少78±3%；在新生细胞中，它使半胱天冬酶活性减少30±3%，TUNEL阳性细胞减少32±7%。在暴露于中性粒细胞的成年心肌细胞中，异氟烷使线粒体细胞色素c和半胱天冬酶活性均减少47±3%，TUNEL阳性细胞减少25±4%。异氟烷增强了磷酸化Akt和Bcl-2的表达。渥曼青霉素和HA14-1阻止了异氟烷的作用（凋亡细胞为53±8%和54±7%，而无阻断剂时为18±1%）。
异氟烷通过激活Akt和增加Bcl-2表达来保护心肌细胞免受缺氧、过氧化氢或活化中性粒细胞诱导的凋亡。这表明细胞凋亡的减少有助于异氟烷的心脏保护作用。
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